Breast cancer is the most common malignancy among women, and has one of the highest fatality rates of all cancers affecting females. In fact, breast cancer remains the leading cause of cancer deaths in women aged 20-59 (Greenlee et al., 2000).
Most breast cancers appear as a slowly growing, painless mass. There are a number of physical signs which might suggest the presence of breast cancer, and these may be discovered through a breast examination. Mammography, xerography, and termography are other established methods of detecting malignant breast masses (Cancroft and Goldsmith, 1973). Breast cancer metastasizes by direct extension, and via the lymphatics and the blood stream. Distant spread of the disease may be confirmed by lymph node biopsy, by x-ray surveys of skeleton and chest, and, when appropriate, by liver and bone scans using radioisotopes. Nevertheless, while history, physical examination, and mammography may strongly suggest breast cancer, a diagnosis can only be made by microscopic examination of tissue removed by excisional biopsy or by aspiration cytology or biopsy. At present, then, there is no means of diagnosing breast cancer in a patient without necessitating the removal of tissue.
Regarding treatment, breast cancer therapy depends mainly on the extent of the disease and the patient""s age. There are a number of methods currently used to treat breast cancer, including surgery, radiotherapy, hormone therapy, and chemotherapy. Successful cancer therapy is directed to the primary tumor and to any metastases, whether clinically apparent or microscopic. Because breast tumors may be cured with combined modality therapy, each of the above methods may be used alone, or in conjunction with one or more other therapies. Thus, local and regional therapy, surgery, or radiotherapy is often integrated with systemic therapy (e.g., chemotherapy). Adjunctive chemotherapy, in particular, has a definite role in the treatment of patients with breast cancer and axillary lymph node involvement.
When there is no evidence that cancer has spread peripherally from the breast, the treatment most often recommended is surgery, namely, a mastectomy. Many, if not most, primary operable Stage I and Stage II breast carcinomas can be conservatively managed by partial mastectomy (lumpectomy) plus a standard axillary node dissection, followed by irradiation of the remaining breast tissue. Chemotherapy is sometimes used as an adjuvant to surgery. Radiotherapy may also be used as an adjuvant to surgery, particularly in conjunction with a partial mastectomy and a standard axillary node dissection. For recurrent cancer, palliative radiotherapy can be valuable in controlling local chest wall or cervical lymph node recurrences, and in relieving pain from skeletal metastases.
Hormone therapy, by addition or subtraction, is of greatest use in the palliation of symptoms of breast cancer, or in delaying advance of the disease. Hormone therapy is often combined with radiotherapy when cancer recurs following mastectomy, and when the tumor is so advanced that surgery is contra-indicated or only palliative. The presence or absence of estrogen- and progesterone-receptor protein in primary or metastatic tumor tissue is used to predict which patients may be expected to respond to additive or ablative hormone therapy (Thorpe, 1976).
Cytotoxic chemotherapy is an additional method currently used in the treatment of breast cancer. Prophylactic chemotherapy may be useful in patients at high risk of developing recurrent cancer (i.e., those with axillary lymph node metastases). Chemotherapy is also used in patients with recurrent breast cancer, sometimes in conjunction with hormonal manipulations and/or tamoxifen. The most commonly used, and most effective, chemotherapeutic agent is 5-fluorouracil. Chemotherapeutic agents have demonstrated value in halting or delaying the appearance of metastases, especially in premenopausal patients, and in treating recurrences.
Despite the various mechanisms for detecting, diagnosing, and treating breast cancer, the disease remains the most common cancer in women, and is one of the most fatal (Greenlee et al., 2000). Clearly, alternative strategies for detection of micrometastatic disease, and for more effective and targeted systemic therapies, are needed to improve survival in breast cancer patients. Accordingly, new methods of diagnosis and treatment of breast cancer are still needed, and would be welcome additions to the arsenal of methods currently used in the fight against breast cancer.
The present invention is based upon the discovery that mammary gland sodium/iodide (Na+/Ixe2x88x92) symporter (mgNIS), a glycoprotein that catalyzes the active transport of iodide, is found in mammary tumoral cells. This discovery has broad implications in the diagnosis and treatment of breast cancer, and in the monitoring of breast cancer therapy.
Accordingly, it is an object of the present invention to provide a method for diagnosing breast cancer in a subject, by detecting expression of mgNIS in breast tissue of the subject.
It is also an object of the present invention to provide a method for treating breast cancer in a subject, by diagnosing breast cancer in the subject by detecting expression of mgNIS in breast tissue of the subject, and treating the breast cancer diagnosed in the subject.
Finally, it is an object of the present invention to provide a method for assessing the efficacy of breast cancer therapy in a subject who has undergone or is undergoing treatment for breast cancer, by monitoring expression of mgNIS in breast tissue of the subject.
Additional objects of the present invention will be apparent from the description which follows.